Constitutive HOXA5 Expression Inhibits Erythropoiesis and Increases Myelopoiesis From Human Hematopoietic Progenitors

摘要: The role of the homeobox gene HOXA5 in normal human hematopoiesis was studied by constitutively expressing cDNA CD34+ and CD34+CD38− cells from bone marrow cord blood. By using retroviral vectors that contained both a cell surface marker gene, pure populations progenitors expressed transgene were obtained for analysis differentiation patterns. Based on immunophenotypic morphological cultures transduced cells, expression caused significant shift toward myeloid away erythroid comparison to with Control ( P = .001, n 15 analysis; < .0001, 19 analysis). Transduction more primitive (CD34+CD38− cells) resulted significantly greater effect than did transduction largely committed population .006 difference between v CD34+CD38−cells). Erythroid (burst-forming unit-erythroid [BFU-E]) decreased frequency among vector .016, 7), no reduction total CFU numbers. Clonal single or control (cultured culture conditions) showed prevented produced clones preponderance undifferentiated blasts. These studies show constitutive inhibits erythropoiesis promotes myelopoiesis. reciprocal inhibition promotion myelopoiesis absence any demonstrable proliferation suggests diverts at mulitpotent progenitor stage pathway.